Researchers Uncover Details of Early Stages in Muscle Formation and Regeneration

Tuesday, January 22, 2013

Researchers Uncover Details of Early Stages in Muscle Formation and Regeneration

Researchers
at the National Institutes of Health
(NIH) have identified proteins that allow muscle cells in mice to form from the
fusion of the early stage cells that give rise to the muscle cells.

The findings have implications for
understanding how to repair and rehabilitate muscle tissue and to understanding
other processes involving cell fusion, such as when a sperm fertilizes an egg,
when viruses infect cells, or when specialized cells called osteoclasts dissolve
and assimilate bone tissue in order to repair and maintain bones.

"Through a process that starts with these progenitor cells, the body
forms tissue that accounts for about one-third of its total weight," said
the study's senior author, Leonid V. Chernomordik, PhD. "Our study
provides the first look at the very early stages of this fusion process."

Muscle cells originate from precursor cells known as myoblasts. Myoblasts
fuse to form a single long tubular cell called a myocyte (a muscle fiber).
Muscle tissue is composed of large collections of these fibers. The fusion of
myoblasts into muscle fibers takes place early in fetal development. With
exercise and throughout a person's life, the process is repeated to form new
muscle mass and repair old or damaged muscle.

It takes many hours for cells to prepare for fusion, but the fusion process
itself is very rapid. To study myoblast fusion, the researchers first blocked
the start of the fusion process with a chemical. Ordinarily, the mouse
myoblasts the researchers worked with fuse at varied intervals. By blocking
fusion, and then lifting the block, the researchers were able to synchronize
fusion in a large number of cells, making the process easier to study.

The researchers identified the 2 distinct stages of cell fusion and the
essential proteins that facilitate these stages.

In the first stage, 2 myoblasts meet, and proteins on cell surface membranes
cause the membranes to meld. In the second stage, a pore opens between the
cells and their contents merge. This second step is guided by proteins inside
the cells. (See graphic
provided by NIH.)

The work identifies 2 cell surface proteins that act at the start of
myoblast fusion. These proteins belong to a large family of proteins called
annexins. Annexins also are known to play a role in membrane repair and in
inflammation.

The researchers identified the protein dynamin, found inside the cell, as essential
to the second stage of the cell fusion process.

"Dynamin also has an unexplained link to certain rare and poorly
understood myopathies—disorders characterized by underdeveloped muscles,"
said Chernomordik. "We hope that further examination of the role of
dynamin in cell fusion will lead to a greater understanding of these
conditions."